Comparison of Point-of-care Produced CAR T-cell With Commercial CAR T-cells in Patients With R/R LBCL — HOVON161  

NHL Clinical Trial

Official title: A Phase II Non-inferiority Study Comparing Point-of-care Produced CAR T-cell to Commercial CAR T-cells in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma

Status Recruiting

Clinical Trial Summary

A phase II, multi-center study to compare the feasibility, and clinical efficacy of local manufacturing of CD19-directed CAR T-cells (ARI-0001 CAR T-cells) with commercial produced CAR T-cells (for example axicabtagene ciloleucel, a CD19 targeting commercially available CAR T-cell) in patients with relapsed or refractory (R/R) DLBCL.

Clinical Trial Description

Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of adoptive cell therapy that has proven its efficacy in the treatment of various hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). CD19 has been the most studied target antigen for CAR T-cell immunotherapy. Anti-CD19 CAR T-cell therapy has shown durable responses in patients with different B-NHLs, including Diffuse Large B-cell Lymphoma (DLBCL).

Unfortunately, up to 50-60% of the patients do not respond to CD19-directed CAR T-cell therapy or relapse. There are several shortcomings of current CD19-directed CAR T-cell therapy, that are likely responsible for therapy failure, namely: i) Due to centralized production at commercial sites, the production is time consuming (about 4 weeks), meaning that patients with rapidly progressive lymphoma may not reach the moment of the infusion of the anti-CD19 CAR T-cells. ii) Furthermore, for the current production processes, the autologous T-cells need to be cryopreserved for shipment from the hospital to the production sites and vice versa. This (double) cryopreservation process can decrease the quality of the CAR T-cells. This trial aims to address these shortcomings and will study the feasibility, and clinical efficacy of local manufacturing of CD19-directed CAR T-cells (ARI-0001 CAR T-cells), in a completely closed system using the CliniMACS Prodigy device. This study will compare the clinical efficacy of locally produced CAR T-cells to commercial produced CAR T-cells (for example axicabtagene ciloleucel, a CD19 targeting commercially available CAR T-cell) in patients with relapsed or refractory (R/R) DLBCL.

This in-house (point-of-care) production process of ARI-0001 will take approximately 12 days and thus will generate CAR T-cells "faster" which will be infused in the patient without cryopreservation ("fresh"). Furthermore, the point-of-care production process can be replicated in academic institutions with the appropriate cellular manufacturing facilities. If successful, this study will show feasibility of local production of CAR T-cell therapy, improving their rapid accessibility and quality. ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• NHL

• NCT number: NCT05641428
• Study type: Interventional
• Source: University Medical Center Groningen
• Contact: T. (Tom) van Meerten
• Phone: +31 (0)10 7041560
• Email: hdc@erasmusmc.nl
• Status: Recruiting
• Phase: Phase 2
• Start date: October 18, 2022
• Completion date: December 2027